479 research outputs found
A new perspective on metformin therapy in type 1 diabetes
Metformin is quite frequently used off-label in type 1 diabetes to limit insulin dose requirement. Guidelines recommend that it can improve glucose control in those who are overweight and obese but evidence in support of this is limited. Recently-published findings from the REducing with MetfOrmin Vascular Adverse Lesions (REMOVAL) trial suggest that metformin therapy in type 1 diabetes can reduce atherosclerosis progression, weight and LDL-cholesterol levels. This provides a new perspective on metformin therapy in type 1 diabetes and suggests a potential role for reducing the long-term risk of cardiovascular disease
Diabetes, hypertension, and cardiovascular disease: clinical insights and vascular mechanisms
Hypertension and type 2 diabetes are common comorbidities. Hypertension is twice as frequent in patients with diabetes compared with those who do not have diabetes. Moreover, patients with hypertension often exhibit insulin resistance and are at greater risk of diabetes developing than are normotensive individuals. The major cause of morbidity and mortality in diabetes is cardiovascular disease, which is exacerbated by hypertension. Accordingly, diabetes and hypertension are closely interlinked because of similar risk factors, such as endothelial dysfunction, vascular inflammation, arterial remodelling, atherosclerosis, dyslipidemia, and obesity. There is also substantial overlap in the cardiovascular complications of diabetes and hypertension related primarily to microvascular and macrovascular disease. Common mechanisms, such as upregulation of the renin-angiotensin-aldosterone system, oxidative stress, inflammation, and activation of the immune system likely contribute to the close relationship between diabetes and hypertension. In this article we discuss diabetes and hypertension as comorbidities and discuss the pathophysiological features of vascular complications associated with these conditions. We also highlight some vascular mechanisms that predispose to both conditions, focusing on advanced glycation end products, oxidative stress, inflammation, the immune system, and microRNAs. Finally, we provide some insights into current therapies targeting diabetes and cardiovascular complications and introduce some new agents that may have vasoprotective therapeutic potential in diabetes
Metformin and cardiorenal outcomes in diabetes : a reappraisal
The guidance issued to the pharmaceutical industry by the US Food and Drug Administration in 2008 has led to the publication of a series of randomised, controlled cardiovascular outcomes trials with newer therapeutic classes of glucoseâlowering medications. Several of these trials, which evaluated the newer therapeutic classes of SGLT2 inhibitors and GLPâ1 receptor agonists have reported a reduced incidence of major adverse cardiovascular and/or renal outcomes, usually relative to placebo and standard of care. Metformin was the first glucoseâlowering agent reported to improve cardiovascular outcomes in the UK Prospective diabetes Study (UKPDS) and thus became the foundation of standard care. However, as this clinical trial reported more than 20âyears ago, differences from current standards of trial design and evaluation complicate comparison of the cardiovascular profiles of older and newer agents. Our article revisits the evidence for cardiovascular protection with metformin and reviews its effects on the kidney.Publisher PDFPeer reviewe
Cardiovascular benefits of GLP-1 agonists in type 2 diabetes: a comparative review
Type 2 diabetes (T2D) carries risks of both cardiovascular (CV) (myocardial infarction, stroke, and peripheral vascular disease) and microvascular (retinopathy/nephropathy/neuropathy) complications. Glucose-lowering is an effective strategy for preventing microvascular complications, but the extent to which it can reduce CV complications is less certain. Glucagon-like peptide-1 (GLP-1) agonists are potent glucose-lowering agents but also have potentially beneficial effects on other traditional (body weight, blood pressure (BP), and LDL cholesterol) and non-traditional risk factors (low grade inflammation and endothelial dysfunction). The results of four large CV outcome trials with GLP-1 agonists are now available. These have compared lixisenatide (ELIXA), liraglutide (LEADER), semaglutide (SUSTAIN-6), and long-acting exenatide (EXSCEL) with placebo and standard of care over 2â4 years; four others (including with dulaglutide and albiglutide) are ongoing. LEADER and SUSTAIN-6 have demonstrated reductions in rates of major adverse CV events with active GLP-1 treatment but ELIXA and EXSCEL have not. In this review, we discuss the mechanisms by which GLP-1 receptor agonists act on the CV system and the design and conduct of these trials. Contrary to the assertions that (a) all GLP-1 agonists reduce CV disease in T2D but to different extents or (b) the magnitude of CV protection is predominantly related to glucose-lowering, we argue that CV benefit is specific to agents that provide longer acting agonism at the GLP-1 receptor. The mechanisms involve reduction in body weight and BP, and lowering of LDL-cholesterol and glucose, but pleiotropic effectsâincluding suppression of low grade inflammation, vasodilation, and natriuresisâare also likely relevant
Metformin, lipids and atherosclerosis prevention
Purpose of review: We provide an overview of recent publications that extend clinically relevant knowledge relating to metformin's effects on lipids and atherosclerotic vascular disease and/or provide insights into the drug's mechanisms of action on the heart and vasculature.
Recent findings: We focus on original research in humans or in human tissues. Several recently completed randomized clinical trials have reported effects of metformin on surrogate measures of atherosclerotic vascular disease, including carotidâintima media thickness, vascular reactivity and calcification in people with Type 1 (T1D) and Type 2 (T2D) diabetes as well as nondiabetic dysglycaemia. In addition, observational studies have provided novel insights into the mechanisms of metformin's effects on carotid plaque, monocytes/macrophages, vascular smooth muscle and endothelial cells, including via 5â-adenosine monophosphate-activated protein kinase (AMPK) activation.
Summary: Recent trials based on surrogate outcome measures have provided further data suggesting protective effects of metformin against vascular disease in youth and adults with Type 1 diabetes, as well as in adults with prediabetes and Type 2 diabetes. In parallel, human tissue and cell studies have provided new insights into pleiotropic effects of metformin and suggest novel drug targets. As metformin is an inexpensive agent with an established safety profile, larger scale clinical trials based on hard clinical outcomes [cardiovascular disease (CVD) events] are now indicated
Improving the clinical value and utility of CGM systems: issues and recommendations: a joint statement of the European Association for the Study of Diabetes and the American Diabetes Association Diabetes Technology Working Group
The first systems for continuous glucose monitoring (CGM) became available over 15 years ago. Many then believed CGM would revolutionize the use of intensive insulin therapy in diabetes; however, progress toward that vision has been gradual. Although increasing, the proportion of individuals using CGM rather than conventional systems for self-monitoring of blood glucose on a daily basis is still low in most parts of the world. Barriers to uptake include cost, measurement reliability (particularly with earlier-generation systems), human factors issues, lack of a standardized format for displaying results, and uncertainty on how best to use CGM data to make therapeutic decisions. This Scientific Statement makes recommendations for systemic improvements in clinical use and regulatory (pre- and postmarketing) handling of CGM devices. The aim is to improve safety and efficacy in order to support the advancement of the technology in achieving its potential to improve quality of life and health outcomes for more people with diabetes
Improving the clinical value and utility of CGM systems: issues and recommendations : a joint statement of the European Association for the Study of Diabetes and the American Diabetes Association Diabetes Technology Working Group
The first systems for continuous glucose monitoring (CGM) became available over 15Â years ago. Many then believed CGM would revolutionise the use of intensive insulin therapy in diabetes; however, progress towards that vision has been gradual. Although increasing, the proportion of individuals using CGM rather than conventional systems for self-monitoring of blood glucose on a daily basis is still low in most parts of the world. Barriers to uptake include cost, measurement reliability (particularly with earlier-generation systems), human factors issues, lack of a standardised format for displaying results and uncertainty on how best to use CGM data to make therapeutic decisions. This scientific statement makes recommendations for systemic improvements in clinical use and regulatory (pre- and postmarketing) handling of CGM devices. The aim is to improve safety and efficacy in order to support the advancement of the technology in achieving its potential to improve quality of life and health outcomes for more people with diabetes
Left ventricular outcomes following multivessel PCI vs. infarct artery-only PCI in patients with acute STEMI: the Glasgow PRAMI CMR sub-study
No abstract available
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